Transglutaminase 2 Regulates HSF1 Gene Expression in the Acute Phase of Fish Optic Nerve Regeneration

• Published in: International journal of molecular sciences Vol. 25; no. 16; p. 9078
• Main Authors: Sugitani, Kayo, Mokuya, Takumi, Kanai, Yu, Takaya, Yurina, Omori, Yuya, Koriyama, Yoshiki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.08.2024; MDPI
• Subjects: Acids; Animals; Antibodies; Cytochrome; Dehydrogenases; Enzymes; Gene expression; Gene Expression Regulation - drug effects; Genetic testing; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Heat Shock Transcription Factors - genetics; Heat Shock Transcription Factors - metabolism; HSF1; Klf4; Nerve Regeneration - genetics; Oct4; Optic nerve; Optic Nerve - metabolism; Optic Nerve Injuries - genetics; Optic Nerve Injuries - metabolism; Protein Glutamine gamma Glutamyltransferase 2 - metabolism; Proteins; Retina; Retinal Ganglion Cells - metabolism; Signal Transduction; Sox2; Stem cells; TG2; Transglutaminases - genetics; Transglutaminases - metabolism; Tretinoin - metabolism; Tretinoin - pharmacology; Yamanaka factors; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Oct4; Sox2; Yamanaka factors; cell survival; retina; HSF1; optic nerve regeneration; zebrafish; Klf4; TG2
• ISSN: 1661-6596; 1422-0067; 1422-0067
• DOI: 10.3390/ijms25169078

Fish retinal ganglion cells (RGCs) can regenerate after optic nerve lesions (ONLs). We previously reported that heat shock factor 1 (HSF1) and Yamanaka factors increased in the zebrafish retina 0.5-24 h after ONLs, and they led to cell survival and the transformation of neuro-stem cells. We also showed that retinoic acid (RA) signaling and transglutaminase 2 (TG2) were activated in the fish retina, performing neurite outgrowth 5-30 days after ONLs. In this study, we found that RA signaling and TG2 increased within 0.5 h in the zebrafish retina after ONLs. We examined their interaction with the TG2-specific morpholino and inhibitor due to the significantly close initiation time of TG2 and HSF1. The inhibition of TG2 led to the complete suppression of HSF1 expression. Furthermore, the results of a ChIP assay with an anti-TG2 antibody evidenced significant anti-TG2 immunoprecipitation of HSF1 genome DNA after ONLs. The inhibition of TG2 also suppressed Yamanaka factors' gene expression. This rapid increase in TG2 expression occurred 30 min after the ONLs, and RA signaling occurred 15 min before this change. The present study demonstrates that TG2 regulates Yamanaka factors via HSF1 signals in the acute phase of fish optic nerve regeneration.